An aim of modern medicine is to provide personalized or individualized treatment regimens. Those are treatment regimens which take into account a patient's individual needs or risks. A particularly important risk is the presence of a cardiovascular complication, particularly an unrecognized cardiovascular complication.
Cardiovascular complications, particularly heart diseases, are the leading cause of morbidity and mortality in the Western hemisphere. It is known that cardiovascular complications can result from certain medications, e.g. anthracycline treatment, that show cardiotoxic effects. In many cases, the risk associated with cardiotoxic medication is dose-limiting.
The use of natriuretic peptides as molecular or biochemical markers is known as such. In WO 02/089657, it has been suggested to measure brain natriuretic peptide (BNP) to diagnose myocardial infarction. In WO 02/083913 it has been suggested to use BNP to predict near-term morbidity or mortality in patients with congestive heart failure, myocardial infarction, ST-elevated myocardial infarction, or non-ST-elevated acute coronary syndromes.
Suzuki et al. have investigated whether anthracyclines can influence the plasma concentration of BNP (Suzuki, T., et al. (1998). Elevated B-type natriuretic peptide levels after anthracycline administration. American Heart Journal, vol. 136(2), p. 362-363.). The study suggests the possible use of BNP levels to assess the cardiac state after anthracycline administration. According to their interpretation, BNP levels most likely reflect cardiac tolerance to the cardiotoxic agent.
Okumura et al. investigated whether BNP can be used as a predictor of cardiotoxicity in patients with acute leukaemia treated with a daunorubicin-containing regimen (Okumura, H., et al. (2000). Brain natriuretic peptide is a predictor of anthracycline-induced cardiotoxicity. Acta Haematologica, vol. 104, p. 158-163). The authors conclude that their preliminary results suggest that BNP may be useful as an early and sensitive indicator of anthracycline induced cardiotoxicity.
However, the value of BNP as a diagnostic marker in the context of cardiotoxicity is still subject to debate. A recent review questions whether BNP can be used to monitor drug-related cardiotoxicity (Mohideen, M. R. (2002), Brain natriuretic peptide is more than a marker. Ceylon Medical Journal, vol. 47(3), p. 81-82). Another recent review, published after the review mentioned beforehand, comes to the conclusion that there are “no encouraging data” concerning the early diagnosis of left ventricular dysfunction using BNP for diagnosing cardiotoxicity caused by anthracyclines (Tsekoura, D. K., et al. (2003). Brain natriuretic peptide. Hellenic Journal of Cardiology, vol. 44, p. 266-270).
The role of NT-proBNP for diagnosis of cardiotoxicity mediated by anthracyclines has not been subject to investigation.
Furthermore, the prior art relates only to a potential use of BNP for monitoring cardiotoxicity, i.e. cardiotoxicity caused by a drug after treatment has already commenced.
However, it would be preferable if risk patients could be identified even before they receive cardiotoxic medication. It is important to realize that cardiovascular complications can remain asymptomatic for long periods of time. Therefore, reliable diagnosis of the presence of a cardiovascular complication is more difficult and error-prone than generally believed (Svendstrup Nielsen, L., et al. (2003). N-terminal pro-brain natriuretic peptide for discriminating between cardiac and non-cardiac dyspnoea. The European Journal of Heart Failure).
Currently, only patients with a known history of heart disease or hypertension receive closer monitoring in case of a treatment with cardiotoxic medication. In particular, general practitioners and non-cardiologists have no simple means to identify a previously unrecognized cardiovascular problem.
Therefore, there is a need to for a method or means to identify risk patients before they receive cardiotoxic medication. Particularly, there is a need to provide a suitable diagnostic means. Particularly, there is a need for a diagnostic means that allows to identify risk patients that have no history of a cardiovascular complication. In particular, the diagnostic means should be simple, fast, reliable and suited for use by general practitioners and non-cardiologists. Accordingly, it is the object of the present invention to provide such means and methods.